Spaceflight tracking and data network operational reliability computer output for MTBF and availability. Appendix V to CSC-1-395

Tables of data are provided to show the availability of Skylab data to selected ground stations during the phases of Skylab preflight, Skylab unmanned condition, and Skylab manned condition. The mean time between failure (MTBF) of the same Skylab functions is tabulated for the selected ground stations. All reliability data are based on a 90 percent confidence interval

Spaceflight tracking and data network operational reliability assessment for Skylab

Data on the spaceflight communications equipment status during the Skylab mission were subjected to an operational reliability assessment. Reliability models were revised to reflect pertinent equipment changes accomplished prior to the beginning of the Skylab missions. Appropriate adjustments were made to fit the data to the models. The availabilities are based on the failure events resulting in the stations inability to support a function of functions and the MTBF's are based on all events including 'can support' and 'cannot support'. Data were received from eleven land-based stations and one ship

Clinical, biochemical and genetic spectrum of 70 patients with ACAD9 deficiency: Is riboflavin supplementation effective?

Background: Mitochondrial acyl-CoA dehydrogenase family member 9 (ACAD9) is essential for the assembly of mitochondrial respiratory chain complex I. Disease causing biallelic variants in ACAD9 have been reported in individuals presenting with lactic acidosis and cardiomyopathy. Results: We describe the genetic, clinical and biochemical findings in a cohort of 70 patients, of whom 29 previously unpublished. We found 34 known and 18 previously unreported variants in ACAD9. No patients harbored biallelic loss of function mutations, indicating that this combination is unlikely to be compatible with life. Causal pathogenic variants were distributed throughout the entire gene, and there was no obvious genotype-phenotype correlation. Most of the patients presented in the first year of life. For this subgroup the survival was poor (50% not surviving the first 2 years) comparing to patients with a later presentation (more than 90% surviving 10 years). The most common clinical findings were cardiomyopathy (85%), muscular weakness (75%) and exercise intolerance (72%). Interestingly, severe intellectual deficits were only reported in one patient and

The Power Board of the KM3NeT Digital Optical Module: design, upgrade, and production

The KM3NeT Collaboration is building an underwater neutrino observatory at the bottom of the Mediterranean Sea consisting of two neutrino telescopes, both composed of a three-dimensional array of light detectors, known as digital optical modules. Each digital optical module contains a set of 31 three inch photomultiplier tubes distributed over the surface of a 0.44 m diameter pressure-resistant glass sphere. The module includes also calibration instruments and electronics for power, readout and data acquisition. The power board was developed to supply power to all the elements of the digital optical module. The design of the power board began in 2013, and several prototypes were produced and tested. After an exhaustive validation process in various laboratories within the KM3NeT Collaboration, a mass production batch began, resulting in the construction of over 1200 power boards so far. These boards were integrated in the digital optical modules that have already been produced and deployed, 828 until October 2023. In 2017, an upgrade of the power board, to increase reliability and efficiency, was initiated. After the validation of a pre-production series, a production batch of 800 upgraded boards is currently underway. This paper describes the design, architecture, upgrade, validation, and production of the power board, including the reliability studies and tests conducted to ensure the safe operation at the bottom of the Mediterranean Sea throughout the observatory's lifespa

Mitochondrial ATP synthase: architecture, function and pathology

Human mitochondrial (mt) ATP synthase, or complex V consists of two functional domains: F1, situated in the mitochondrial matrix, and Fo, located in the inner mitochondrial membrane. Complex V uses the energy created by the proton electrochemical gradient to phosphorylate ADP to ATP. This review covers the architecture, function and assembly of complex V. The role of complex V di-and oligomerization and its relation with mitochondrial morphology is discussed. Finally, pathology related to complex V deficiency and current therapeutic strategies are highlighted. Despite the huge progress in this research field over the past decades, questions remain to be answered regarding the structure of subunits, the function of the rotary nanomotor at a molecular level, and the human complex V assembly process. The elucidation of more nuclear genetic defects will guide physio(patho)logical studies, paving the way for future therapeutic interventions

Embedded Software of the KM3NeT Central Logic Board

The KM3NeT Collaboration is building and operating two deep sea neutrino telescopes at the bottom of the Mediterranean Sea. The telescopes consist of latices of photomultiplier tubes housed in pressure-resistant glass spheres, called digital optical modules and arranged in vertical detection units. The two main scientific goals are the determination of the neutrino mass ordering and the discovery and observation of high-energy neutrino sources in the Universe. Neutrinos are detected via the Cherenkov light, which is induced by charged particles originated in neutrino interactions. The photomultiplier tubes convert the Cherenkov light into electrical signals that are acquired and timestamped by the acquisition electronics. Each optical module houses the acquisition electronics for collecting and timestamping the photomultiplier signals with one nanosecond accuracy. Once finished, the two telescopes will have installed more than six thousand optical acquisition nodes, completing one of the more complex networks in the world in terms of operation and synchronization. The embedded software running in the acquisition nodes has been designed to provide a framework that will operate with different hardware versions and functionalities. The hardware will not be accessible once in operation, which complicates the embedded software architecture. The embedded software provides a set of tools to facilitate remote manageability of the deployed hardware, including safe reconfiguration of the firmware. This paper presents the architecture and the techniques, methods and implementation of the embedded software running in the acquisition nodes of the KM3NeT neutrino telescopes

Letter of interest for a neutrino beam from Protvino to KM3NeT/ORCA

The Protvino accelerator facility located in the Moscow region, Russia, is in a good position to offer a rich experimental research program in the field of neutrino physics. Of particular interest is the possibility to direct a neutrino beam from Protvino towards the KM3NeT/ORCA detector, which is currently under construction in the Mediterranean Sea 40 km offshore Toulon, France. This proposal is known as P2O. Thanks to its baseline of 2595 km, this experiment would yield an unparalleled sensitivity to matter effects in the Earth, allowing for the determination of the neutrino mass ordering with a high level of certainty after only a few years of running at a modest beam intensity of ≈ 90 kW. With a prolonged exposure (≈1500 kWyear), a 2σ sensitivity to the leptonic CP-violating Dirac phase can be achieved. A second stage of the experiment, comprising a further intensity upgrade of the accelerator complex and a densified version of the ORCA detector (Super-ORCA), would allow for up to a 6σ sensitivity to CP violation and a 10º−17º resolution on the CP phase after 10 years of running with a 450 kW beam, competitive with other planned experiments. The initial composition and energy spectrum of the neutrino beam would need to be monitored by a near detector, to be constructed several hundred meters downstream from the proton beam target. The same neutrino beam and near detector set-up would also allow for neutrino-nucleus cross section measurements to be performed. A short-baseline sterile neutrino search experiment would also be possible

Prospects for combined analyses of hadronic emission from γ\gamma-ray sources in the Milky Way with CTA and KM3NeT

The Cherenkov Telescope Array and the KM3NeT neutrino telescopes are major upcoming facilities in the fields of $\gamma$-ray and neutrino astronomy, respectively. Possible simultaneous production of $\gamma$ rays and neutrinos in astrophysical accelerators of cosmic-ray nuclei motivates a combination of their data. We assess the potential of a combined analysis of CTA and KM3NeT data to determine the contribution of hadronic emission processes in known Galactic $\gamma$-ray emitters, comparing this result to the cases of two separate analyses. In doing so, we demonstrate the capability of Gammapy, an open-source software package for the analysis of $\gamma$-ray data, to also process data from neutrino telescopes. For a selection of prototypical $\gamma$-ray sources within our Galaxy, we obtain models for primary proton and electron spectra in the hadronic and leptonic emission scenario, respectively, by fitting published $\gamma$-ray spectra. Using these models and instrument response functions for both detectors, we employ the Gammapy package to generate pseudo data sets, where we assume 200 hours of CTA observations and 10 years of KM3NeT detector operation. We then apply a three-dimensional binned likelihood analysis to these data sets, separately for each instrument and jointly for both. We find that the largest benefit of the combined analysis lies in the possibility of a consistent modelling of the $\gamma$-ray and neutrino emission. Assuming a purely leptonic scenario as input, we obtain, for the most favourable source, an average expected 68% credible interval that constrains the contribution of hadronic processes to the observed $\gamma$-ray emission to below 15%.Comment: 18 pages, 15 figures. Submitted to journa

Searches for neutrinos in the direction of radio-bright blazars with the ANTARES telescope

Active galaxies, especially blazars, are among the most promising neutrino source candidates. To date, ANTARES searches for these objects considered GeV-TeV $\gamma$-ray bright blazars. Here, a statistically complete radio-bright blazar sample is used as the target for searches of origins of neutrinos collected by the ANTARES neutrino telescope over 13 years of operation. The hypothesis of a neutrino-blazar directional correlation is tested by pair counting and by a complementary likelihood-based approach. The resulting post-trial $p$-value is $3.0\%$ ($2.2\sigma$ in the two-sided convention), possibly indicating a correlation. Additionally, a time-dependent analysis is performed to search for temporal clustering of neutrino candidates as a mean of detecting neutrino flares in blazars. None of the investigated sources alone reaches a significant flare detection level. However, the presence of 18 sources with a pre-trial significance above $3\sigma$ indicates a $p=1.4\%$ ($2.5\sigma$ in the two-sided convention) detection of a time-variable neutrino flux. An \textit{a posteriori} investigation reveals an intriguing temporal coincidence of neutrino, radio, and $\gamma$-ray flares of the J0242+1101 blazar at a $p=0.5\%$ ($2.9\sigma$ in the two-sided convention) level. Altogether, the results presented here suggest a possible connection of neutrino candidates detected by the ANTARES telescope with radio-bright blazars

Binding of Pramipexole to Extrastriatal Dopamine D2/D3 Receptors in the Human Brain: A Positron Emission Tomography Study Using 11C-FLB 457

The purpose of this study was to determine the binding sites of pramipexole in extrastriatal dopaminergic regions because its antidepressive effects have been speculated to occur by activating the dopamine D2 receptor subfamily in extrastriatal areas. Dynamic positron emission tomography (PET) scanning using 11C-FLB 457 for quantification of D2/D3 receptor subtype was performed on 15 healthy volunteers. Each subject underwent two PET scans before and after receiving a single dose of pramipexole (0, 0.125, or 0.25 mg). The study demonstrated that pramipexole significantly binds to D2/D3 receptors in the prefrontal cortex, amygdala, and medial and lateral thalamus at a dose of 0.25 mg. These regions have been indicated to have some relation to depression and may be part of the target sites where pramipexole exerts its antidepressive effects